Late-onset anti−NMDA receptor encephalitis
Maarten J. Titulaer, Lindsey McCracken, Iñigo Gabilondo, et al. Neurology published online August 14, 2013 DOI 10.1212/WNL.0b013e3182a4a49c This information is current as of August 14, 2013
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2013 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Published Ahead of Print on August 14, 2013 as 10.1212/WNL.0b013e3182a4a49c
Late-onset anti–NMDA receptor encephalitis
Maarten J. Titulaer, MD, PhD Lindsey McCracken, MPH Iñigo Gabilondo, MD Takahiro Iizuka, MD, PhD Izumi Kawachi, MD, PhD L. Bataller, MD, PhD A. Torrents, BS Myrna R. Rosenfeld, MD, PhD Rita Balice-Gordon, PhD Francesc Graus, MD, PhD Josep Dalmau, MD, PhD
Correspondence to Dr. Dalmau:
[email protected]
ABSTRACT
Objective: To describe the clinical features and outcome of anti–NMDA receptor (NMDAR) encephalitis in patients $45 years old.
Method: Observational cohort study. Results: In a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients $45 years old. Compared with younger adults (18–44 years), older patients were more often male (45% vs 12%, p , 0.0001), had lower frequency of tumors (23% vs 51%, p 5 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p 5 0.009) and treatment (7 vs 4 weeks, p 5 0.039), and had less favorable outcome (modified Rankin Scale score 0–2 at 2 years, 60% vs 80%, p , 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05–0.39, p 5 0.0001), early treatment (OR 0.60, CI 0.47–0.78, p , 0.0001), no need for intensive care (OR 0.09, CI 0.04–0.22, p , 0.0001), and longer follow-up (p , 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10–7.76, p 5 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.
Conclusions: Anti-NMDAR encephalitis is less severe in patients $45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome. Neurology 2013;81:1–6 GLOSSARY CI 5 confidence interval; IQR 5 interquartile range; mRS 5 modified Rankin Scale; NMDAR 5 NMDA receptor; OR 5 odds ratio.
Anti–NMDA receptor (NMDAR) encephalitis is an autoimmune disorder that usually affects children and young adults, resulting in severe neuropsychiatric symptoms that often respond to treatment.1–4 Experience with older patients is limited to a single case report5 and series comprising patients of all ages, but no further information is available. We report a detailed clinical analysis of 31 patients $45 years old and describe several novel features associated with this age group.
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METHODS Patients with immunoglobulin G antibodies against the NR1 subunit of NMDAR were identified from a series of 661 cases with anti-NMDAR encephalitis.2 Detailed information on patients $45 years old, either as individual cases or age group, has not been reported previously. We used 45 years as the cutoff age because a similar threshold has been used in other autoimmune neurologic disorders, like myasthenia gravis. Clinical information was obtained by the authors or referring physicians at the acute stage of the disease.2 Follow-up information was obtained at regular intervals after symptom onset; neurologic status was assessed with the modified Rankin Scale (mRS) score.6 Initial treatment was considered a failure if no sustained improvement occurred within 4 weeks after initiation of immunotherapy or tumor removal, and if the mRS score remained $4.2 Serum and CSF antibody studies were conducted as reported.3 Demographic information and symptoms were analyzed with the Fisher exact test, Fisher-Freeman-Halton test, or Mann-Whitney U test when appropriate, comparing these 31 patients with 338 recently reported patients (aged 18–44 years).2 Because of a skewed From the Department of Neurology (M.J.T., I.G., M.R.R., F.G., J.D.), Hospital Clinic, Universitat de Barcelona/Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Department of Neurology and Neurosciences (M.J.T., L.M., M.R.R., R.B.-G., J.D.), Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (T.I.), Kitasato University School of Medicine, Sagamihara; Department of Neurology (I.K.), Brain Research Institute, Niigata University, Japan; Department of Neurology (L.B.), Hospital Universitario La Fe, Valencia; Biostatistics and Data Management Platform (A.T.), IDIBAPS, Hospital Clinic; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2013 American Academy of Neurology
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2 Characteristics of the patients ‡45 years of age Tumor (time neurologic onset–tumor, wk; removed?)
Treatment
Last mRS First-line (duration Time neurologic therapy of follow-up onset–treatment, wk failure in months)
Time neurologic Prodromal onset–diagnosis, wk symptoms
First symptom
Other symptoms (
